Hydrochloric Acid → 5-Quinolinecarboxylic acid, 7-fluoro-2-(4-fluorophenyl)-1,2,3,4-tetrahydro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-, methyl ester

HRID 1617271Notes

Reaction equation

HRID 1617271 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:27]([O:29][CH3:30])=[O:28])[C:5]2[C:6](=[O:26])[CH:7]([C:20]3[N:24]([CH3:25])[N:23]=[CH:22][N:21]=3)[CH:8]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[N:9](O)[C:10]=2[CH:11]=1.Cl>CO.[Fe]>[F:1][C:2]1[CH:3]=[C:4]([C:27]([O:29][CH3:30])=[O:28])[C:5]2[C:6](=[O:26])[CH:7]([C:20]3[N:24]([CH3:25])[N:23]=[CH:22][N:21]=3)[CH:8]([C:13]3[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=3)[NH:9][C:10]=2[CH:11]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 53353612Methyl 7-fluoro-2-(4-fluorophenyl)-1-hydroxy-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate2×

Product 1

HCID 547529555-Quinolinecarboxylic acid, 7-fluoro-2-(4-fluorophenyl)-1,2,3,4-tetrahydro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-, methyl esterYield 30.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of methyl 7-fluoro-2-(4-fluorophenyl)-1-hydroxy-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (10) (41.4 mg, 0.1 mmol) in methanol (5 mL) was added concentrated HCl solution (w/w 37%, 1 mL) and reductive powdered Fe (56 mg, 1 mmol). The reaction mixture was refluxed for 3 hours. After the disappearance of compound (10) as monitored by LC-MS, the reaction system was partitioned between ethyl acetate (20 mL) and water (20 mL) and then the aqueous phase was extracted with ethyl acetate (10 mL×3). The combined organic phase was dried with Na2SO4, concentrated in vacuo and purified by column chromatography (ethyl acetate:petroleum ether=1:1) to give the title compound (5) as a pale yellow solid (12 mg, yield 30%). LC-MS (ESI) m/z: 399 (M+1)+. 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.58 (s, 3H), 3.87 (s, 3H), 4.17 (d, 1H), 4.87 (s, 1H), 5.38 (d, 1H), 6.50 (dd, 2H), 6.99 (dd, 2H), 7.38 (dd, 2H), 7.80 (s, 1H).

Workup

  1. temperatureThe reaction mixture was refluxed for 3 hours
  2. customthe reaction system was partitioned between ethyl acetate (20 mL) and water (20 mL)
  3. extractionthe aqueous phase was extracted with ethyl acetate (10 mL×3)
  4. dry with materialThe combined organic phase was dried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography (ethyl acetate:petroleum ether=1:1)

Sources & evidence

ORD record
ord-98f8b7f71f334e79959f3be4e340bd16
Source dataset
uspto-grants-2014_07
Patent number
US08765945B2

Reaction notes

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